tbuckley/cabot-search huggingface dataset:
Unequal racial distribution of immunotherapy for late-stage non–small cell lung cancer
Authors: Annie Chang, Raja M Flores, Emanuela Taioli
Journal: JNCI Journal of the National Cancer Institute (2023)

Immunotherapy has increased survival for non-small cell lung cancer (NSCLC), especially for those diagnosed with late-stage disease. However, it is not known if its use is equally distributed across races. We assessed immunotherapy use in 21 098 pathologically confirmed stage IV NSCLC patients according to race in the Surveillance Epidemiology, and End Results-Medicare linked dataset. Multivariable models were conducted to evaluate the independent association of receipt of immunotherapy with race and overall survival according to race. Black patients had statistically significantly lower odds of receiving immunotherapy (adjusted odds ratio = 0.60, 95% confidence interval = 0.44 to 0.80); receipt of immunotherapy was lower in Asian and Hispanic patients but not statistically significant. When immunotherapy was received, survival was similar across races. Immunotherapy for NSCLC is not used equally among races, underscoring the racial disparities that exist in access to the newest cancer treatment. Efforts should be directed toward expanding access to novel, efficacious treatments for advanced stage lung cancer.
The performance of serious games for enhancing attention in cognitively impaired older adults
Authors: Alaa Abd-alrazaq, Israa Abuelezz, Eiman Al-Jafar, Kerstin Denecke, Mowafa Househ, Sarah Aziz, Arfan Ahmed, Ali Aljaafreh, Rawan AlSaad, Javaid Sheikh
Journal: npj Digital Medicine (2023)

Abstract Attention, which is the process of noticing the surrounding environment and processing information, is one of the cognitive functions that deteriorate gradually as people grow older. Games that are used for other than entertainment, such as improving attention, are often referred to as serious games. This study examined the effectiveness of serious games on attention among elderly individuals suffering from cognitive impairment. A systematic review and meta-analyses of randomized controlled trials were carried out. A total of 10 trials ultimately met all eligibility criteria of the 559 records retrieved. The synthesis of very low-quality evidence from three trials, as analyzed in a meta-study, indicated that serious games outperform no/passive interventions in enhancing attention in cognitively impaired older adults ( P &lt; 0.001). Additionally, findings from two other studies demonstrated that serious games are more effective than traditional cognitive training in boosting attention among cognitively impaired older adults. One study also concluded that serious games are better than traditional exercises in enhancing attention. Serious games can enhance attention in cognitively impaired older adults. However, given the low quality of the evidence, the limited number of participants in most studies, the absence of some comparative studies, and the dearth of studies included in the meta-analyses, the results remain inconclusive. Thus, until the aforementioned limitations are rectified in future research, serious games should serve as a supplement, rather than a replacement, to current interventions.
Differential effects of heat-not-burn, electronic, and conventional cigarettes on endothelial glycocalyx
Authors: Ignatios Ikonomidis, Konstantinos Katogiannis, Kallirhoe Kourea, Gavriela Kostelli, George Pavlidis, John Thymis, Eleni Katsanaki, Eirini Maratou, Vaia Lambadiari
Journal:  (2023)
Embedded Bioprinting of Breast Tumor Cells and Organoids Using Low‐Concentration Collagen‐Based Bioinks
Authors: Wen Shi, Sameer Mirza, Mitchell Kuss, Bo Liu, Andrew Hartin, Shibiao Wan, Yunfan Kong, Bhopal Mohapatra, Mena Krishnan, Hamid Band, Vimla Band, Bin Duan
Journal: Advanced Healthcare Materials (2023)

Bioinks for 3D bioprinting of tumor models should not only meet printability requirements but also accurately maintain and support phenotypes of tumor surrounding cells to recapitulate key tumor hallmarks. Collagen is a major extracellular matrix protein for solid tumors, but low viscosity of collagen solution has made 3D bioprinted cancer models challenging. This work produces embedded, bioprinted breast cancer cells and tumor organoid models using low-concentration collagen I based bioinks. The biocompatible and physically crosslinked silk fibroin hydrogel is used to generate the support bath for the embedded 3D printing. The composition of the collagen I based bioink is optimized with a thermoresponsive hyaluronic acid-based polymer to maintain the phenotypes of both the noninvasive epithelial and invasive breast cancer cells, as well as cancer-associated fibroblasts. Mouse breast tumor organoids are bioprinted using optimized collagen bioink to mimic in vivo tumor morphology. A vascularized tumor model is also created using a similar strategy, with significantly enhanced vasculature formation under hypoxia. This study shows the great potential of embedded bioprinted breast tumor models utilizing a low-concentration collagen-based bioink for advancing the understanding of tumor cell biology and facilitating drug discovery research.
Effect of paediatric early warning systems (PEWS) implementation on clinical deterioration event mortality among children with cancer in resource-limited hospitals in Latin America: a prospective, multicentre cohort study
Authors: Asya Agulnik, Hilmarie Muniz-Talavera, Linh T D Pham, Yichen Chen, Angela K Carrillo, Adolfo Cárdenas-Aguirre, Alejandra Gonzalez Ruiz, Marcela Garza, Tania Maria Conde Morelos Zaragoza, Dora Judith Soberanis Vasquez, Alejandra Méndez-Aceituno, Carlos Acuña-Aguirre, Yvania Alfonso-Carreras, Shillel Yahamy Alvarez Arellano, Leticia Aradi Andrade Sarmiento, Rosario Batista, Erika Esther Blasco Arriaga, Patricia Calderon, Mayra Chavez Rios, María Eugenia Costa, Rosdali Díaz-Coronado, Ever Amilcar Fing Soto, Wendy Cristhyna Gómez García, Martha Herrera Almanza, Maria Susana Juarez Tobías, Esmeralda Mercedes León López, Norma Araceli López Facundo, Ruth Angelica Martinez Soria, Kenia Miller, Scheybi Teresa Miralda Méndez, Lupe Nataly Mora Robles, Natalia del Carmen Negroe Ocampo, Berenice Noriega Acuña, Alejandra Osuna Garcia, Carlos M Pérez Alvarado, Clara Krystal Pérez Fermin, Estuardo Enrique Pineda Urquilla, Carlos Andrés Portilla Figueroa, Ligia Estefanía Ríos Lopez, Jocelyn Rivera Mijares, Verónica Soto Chávez, Jorge Iván Suarez Soto, Juliana Teixeira Costa, Isidoro Tejocote Romero, Erika Elena Villanueva Hoyos, Marielba Villegas Pacheco, Meenakshi Devidas, Carlos Rodriguez-Galindo
Journal: The Lancet Oncology (2023)
Efficacy and safety of the <scp>C5</scp> inhibitor crovalimab in complement inhibitor‐naive patients with <scp>PNH</scp> (<scp>COMMODORE</scp> 3): A multicenter, <scp>Phase</scp> 3, single‐arm study
Authors: Hui Liu, Linghui Xia, Jianyu Weng, Fengkui Zhang, Chuan He, Sujun Gao, Jinsong Jia, Alice C. Chang, Pontus Lundberg, Jane Shi, Camelia S. Sima, Alexandre Sostelly, Sasha Sreckovic, Zhenyu Xiao, Zilu Zhang, Rong Fu
Journal: American Journal of Hematology (2023)

Abstract The Phase 3 single‐arm COMMODORE 3 study ( ClinicalTrials.gov , NCT04654468) evaluated efficacy and safety of crovalimab (novel C5 inhibitor) in complement inhibitor‐naive patients with paroxysmal nocturnal hemoglobinuria (PNH). COMMODORE 3 enrolled patients from five China centers. Eligible complement inhibitor‐naive patients with PNH were ≥12 years old, had lactate dehydrogenase (LDH) ≥2 × upper limit of normal (ULN), and had ≥4 transfusions of packed red blood cells within the prior 12 months. Patients received crovalimab loading doses (one intravenous, four subcutaneous) and subsequent every‐4‐weeks subcutaneous maintenance doses per weight‐based tiered‐dosing schedule. Co‐primary efficacy endpoints were mean proportion of patients with hemolysis control (LDH ≤1.5 × ULN) from Week (W)5 through W25 and difference in proportion of patients with transfusion avoidance from baseline through W25 versus within 24 weeks of prescreening in patients who had ≥1 crovalimab dose and ≥1 central LDH assessment after first dose. Between March 17 and August 24, 2021, 51 patients (15–58 years old) were enrolled; all received treatment. At primary analysis, both co‐primary efficacy endpoints were met. Estimated mean proportion of patients with hemolysis control was 78.7% (95% CI: 67.8–86.6). Difference between proportion of patients with transfusion avoidance from baseline through W25 (51.0%; n = 26) versus within 24 weeks of prescreening (0%) was statistically significant ( p &lt; .0001). No adverse events led to treatment discontinuation. One treatment‐unrelated death (subdural hematoma following a fall) occurred. In conclusion, crovalimab, with every‐4‐weeks subcutaneous dosing is efficacious and well tolerated in complement inhibitor‐naive patients with PNH.
Artificial intelligence‐generated peripheral blood film images using generative adversarial networks and diffusion models
Authors: Bingwen Eugene Fan, Ngai Tung Eric Kwok, David Tao Yi Chen, Ponnudurai Kuperan, Siti Thuraiya Binte Abdul Latiff, Moh Sim Wong, Yi Xiong Ong, Kian Guan Eric Lim, Wei Yong Kevin Wong, Shu Ping Lim, Bryan Song Jun Yong, Hemalatha Shanmugam, Yuan Shan Neo, Yi Pin Joshua Ong, Stefan Winkler
Journal: American Journal of Hematology (2023)

The authors declare no conflict of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request. IMAGE S1. Artificially generated images of blood cells from open-source text-to image generators. (A and B) DALL·E2 (OpenAI) (Text-to-image generated microscopic fields of "nucleated cells" and "red blood cells"). (C) Microsoft Bing's Text-to-image generated computer graphic of 2 overlapping lymphocytes amongst red cells. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
The decision aid is the easy part: workflow challenges of shared decision making in cancer care
Authors: Megan E Salwei, Jessica S Ancker, Matthew B Weinger
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Delivering high-quality, patient-centered cancer care remains a challenge. Both the National Academy of Medicine and the American Society of Clinical Oncology recommend shared decision making to improve patient-centered care, but widespread adoption of shared decision making into clinical care has been limited. Shared decision making is a process in which a patient and the patient’s health-care professional weigh the risks and benefits of different options and come to a joint decision on the best course of action for that patient on the basis of their values, preferences, and goals for care. Patients who engage in shared decision making report higher quality of care, whereas patients who are less involved in these decisions have statistically significantly higher decisional regret and are less satisfied. Decision aids can improve shared decision making—for example, by eliciting patient values and preferences that can then be shared with clinicians and by providing patients with information that may influence their decisions. However, integrating decision aids into the workflows of routine care is challenging. In this commentary, we explore 3 workflow-related barriers to shared decision making: the who, when, and how of decision aid implementation in clinical practice. We introduce readers to human factors engineering and demonstrate its potential value to decision aid design through a case study of breast cancer surgical treatment decision making. By better employing the methods and principles of human factors engineering, we can improve decision aid integration, shared decision making, and ultimately patient-centered cancer outcomes.
A phase 1/2 study of azacitidine, venetoclax and pevonedistat in newly diagnosed secondary AML and in MDS or CMML after failure of hypomethylating agents
Authors: Nicholas J. Short, Muharrem Muftuoglu, Faustine Ong, Lewis Nasr, Walid Macaron, Guillermo Montalban-Bravo, Yesid Alvarado, Mahesh Basyal, Naval Daver, Courtney D. Dinardo, Gautam Borthakur, Nitin Jain, Maro Ohanian, Elias Jabbour, Ghayas C. Issa, Wei Qiao, Xuelin Huang, Rashmi Kanagal-Shamanna, Keyur P. Patel, Prithviraj Bose, Farhad Ravandi, Ricardo Delumpa, Regina Abramova, Guillermo Garcia-Manero, Michael Andreeff, Jorge Cortes, Hagop Kantarjian
Journal: Journal of Hematology & Oncology (2023)

Abstract Background Pevonedistat is a first-in-class, small molecular inhibitor of NEDD8-activating enzyme that has clinical activity in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Preclinical data suggest synergy of pevonedistat with azacitidine and venetoclax. Methods This single-center, phase 1/2 study evaluated the combination of azacitidine, venetoclax and pevonedistat in older adults with newly diagnosed secondary AML or with MDS or chronic myelomonocytic leukemia (CMML) after failure of hypomethylating agents. Patients received azacitidine 75 mg/m 2 IV on days 1–7, venetoclax at maximum dose of 200-400 mg orally on days 1–21 (AML cohort) or days 1–14 (MDS/CMML cohort) and pevonedistat 20 mg/m 2 IV on days 1, 3 and 5 for up to 24 cycles. The primary endpoints for the phase 2 portion of the study were the CR/CRi rate in the AML cohort and the overall response rate (CR + mCR + PR + HI) in the MDS/CMML cohort. Findings Forty patients were enrolled (32 with AML and 8 with MDS/CMML). In the AML cohort, the median age was 74 years (range 61–86 years), and 27 patients (84%) had at least one adverse risk cyto-molecular feature, including 15 (47%) with a TP53 mutation or MECOM rearrangement; seventeen patients (53%) had received prior therapy for a preceding myeloid disorder. The CR/CRi rate was 66% (CR 50%; CRi 16%), and the median overall survival (OS) was 8.1 months. In the MDS/CMML cohort, 7 patients (87%) were high or very high risk by the IPSS-R. The overall response rate was 75% (CR 13%; mCR with or without HI 50%; HI 13%). The most common grade 3–4 adverse events were infection in 16 patients (35%), febrile neutropenia in 10 patients (25%) and hypophosphatemia in 9 patients (23%). In an exploratory analysis, early upregulation of NOXA expression was observed, with subsequent decrease in MCL-1 and FLIP, findings consistent with preclinical mechanistic studies of pevonedistat. Upregulation of CD36 was observed, which may have contributed to therapeutic resistance. Conclusions The triplet combination of azacitidine, venetoclax and pevonedistat shows encouraging activity in this very poor-risk population of patients with AML, MDS or CMML. Trial registration ClinicalTrials.gov (NCT03862157).
Combined proteomics and CRISPR‒Cas9 screens in PDX identify ADAM10 as essential for leukemia in vivo
Authors: Ehsan Bahrami, Jan Philipp Schmid, Vindi Jurinovic, Martin Becker, Anna-Katharina Wirth, Romina Ludwig, Sophie Kreissig, Tania Vanessa Duque Angel, Diana Amend, Katharina Hunt, Rupert Öllinger, Roland Rad, Joris Maximilian Frenz, Maria Solovey, Frank Ziemann, Matthias Mann, Binje Vick, Christian Wichmann, Tobias Herold, Ashok Kumar Jayavelu, Irmela Jeremias
Journal: Molecular Cancer (2023)

Acute leukemias represent deadly malignancies that require better treatment. As a challenge, treatment is counteracted by a microenvironment protecting dormant leukemia stem cells.To identify responsible surface proteins, we performed deep proteome profiling on minute numbers of dormant patient-derived xenograft (PDX) leukemia stem cells isolated from mice. Candidates were functionally screened by establishing a comprehensive CRISPR‒Cas9 pipeline in PDX models in vivo.A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) was identified as an essential vulnerability required for the survival and growth of different types of acute leukemias in vivo, and reconstitution assays in PDX models confirmed the relevance of its sheddase activity. Of translational importance, molecular or pharmacological targeting of ADAM10 reduced PDX leukemia burden, cell homing to the murine bone marrow and stem cell frequency, and increased leukemia response to conventional chemotherapy in vivo.These findings identify ADAM10 as an attractive therapeutic target for the future treatment of acute leukemias.
Unresolved questions in selection of therapies for treatment-naïve chronic lymphocytic leukemia
Authors: Rory Bennett, Mary Ann Anderson, John F. Seymour
Journal: Journal of Hematology & Oncology (2023)

Abstract Background The treatment landscape for chronic lymphocytic leukemia (CLL) continues to undergo considerable evolution. Optimal selection of initial therapy from multiple effective options provides a major challenge for clinicians, who need to consider both disease and patient factors in conjunction with a view to sequencing available therapies in event of disease relapse. Review We explore the most topical clinically relevant unresolved questions through discussion of important available pertinent literature and propose expert opinion based on these data. (1) Shrinking role of chemoimmunotherapy (CIT); while novel therapies are generally superior, we highlight the utility of FCR for IGHV-mutated CLL. (2) Choosing between inhibitors of Bruton’s tyrosine kinase (BTKi); while efficacy between agents is likely similar there are important differences in toxicity profiles, including the incidence of cardiac arrhythmia and hypertension. (3) BTKi with or without anti-CD20 monoclonal antibodies (mAb); while obinutuzumab-acalabrutinib (AO) may confer superior progression-free survival to acalabrutinib (Acala), this is not true of rituximab (Ritux) to ibrutinib (Ib)—we highlight that potential for increased side effects should be carefully considered. (4) Continuous BTKi versus time-limited venetoclax-obinutuzumab (VenO); we propose that venetoclax (Ven)-based therapy is generally preferable to BTKi with exception of TP53 aberrant disease. (5) BTKi-Ven versus VenO as preferred time-limited therapy; we discuss comparable efficacies and the concerns about simultaneous 1L exposure to both BTKi and Ven drug classes. (6) Utility of triplet therapy (BTKi-Ven-antiCD20 mAb) versus VenO; similar rates of complete response are observed yet with greater potential for adverse events. (7) Optimal therapy for TP53 aberrant CLL; while limited data are available, there are likely effective novel therapy combinations for TP53 aberrant disease including BTKi, BTKi-Ven ± antiCD20 mAb. Conclusion Frontline therapy for CLL should be selected based on efficacy considering the patient specific biologic profile of their disease and potential toxicities, considering patient comorbidities and preferences. With the present paradigm of sequencing effective agents, 1L combinations of novel therapies should be used with caution in view of potential adverse events and theoretical resistance mechanism concerns in the absence of compelling randomized data to support augmented efficacy.
Copper Ion‐Modified Germanium Phosphorus Nanosheets Integrated with an Electroactive and Biodegradable Hydrogel for Neuro‐Vascularized Bone Regeneration
Authors: Yan Xu, Chao Xu, Kun Yang, Liang Ma, Gaocai Li, Yunsong Shi, Xiaobo Feng, Lei Tan, Deyu Duan, Zhiqiang Luo, Cao Yang
Journal: Advanced Healthcare Materials (2023)

Severe bone defects accompanied by vascular and peripheral nerve injuries represent a huge orthopedic challenge and are often accompanied by the risk of infection. Thus, biomaterials with antibacterial and neurovascular regeneration properties are highly desirable. Here, a newly designed biohybrid biodegradable hydrogel (GelMA) containing copper ion-modified germanium-phosphorus (GeP) nanosheets, which act as neuro-vascular regeneration and antibacterial agents, is designed. The copper ion modification process serves to improve the stability of the GeP nanosheets and offers a platform for the sustained release of bioactive ions. Study findings show that GelMA/GeP@Cu has effective antibacterial properties. The integrated hydrogel can significantly boost the osteogenic differentiation of bone marrow mesenchymal stem cells, facilitate angiogenesis in human umbilical vein endothelial cells, and up-regulate neural differentiation-related proteins in neural stem cells in vitro. In vivo, in the rat calvarial bone defect mode, the GelMA/GeP@Cu hydrogel is found to enhance angiogenesis and neurogenesis, eventually contributing to bone regeneration. These findings indicate that in the field of bone tissue engineering, GelMA/GeP@Cu can serve as a valuable biomaterial for neuro-vascularized bone regeneration and infection prevention.
PAIP 2020: Microsatellite instability prediction in colorectal cancer
Authors: Kyungmo Kim, Kyoungbun Lee, Sungduk Cho, Dong Un Kang, Seongkeun Park, Yunsook Kang, Hyunjeong Kim, Gheeyoung Choe, Kyung Chul Moon, Kyu Sang Lee, Jeong Hwan Park, Choyeon Hong, Ramin Nateghi, Fattaneh Pourakpour, Xiyue Wang, Sen Yang, Seyed Alireza Fatemi Jahromi, Aliasghar Khani, Hwa-Rang Kim, Doo-Hyun Choi, Chang Hee Han, Jin Tae Kwak, Fan Zhang, Bing Han, David Joon Ho, Gyeong Hoon Kang, Se Young Chun, Won-Ki Jeong, Peom Park, Jinwook Choi
Journal: Medical Image Analysis (2023)

Microsatellite instability (MSI) refers to alterations in the length of simple repetitive genomic sequences. MSI status serves as a prognostic and predictive factor in colorectal cancer. The MSI-high status is a good prognostic factor in stage II/III cancer, and predicts a lack of benefit to adjuvant fluorouracil chemotherapy in stage II cancer but a good response to immunotherapy in stage IV cancer. Therefore, determining MSI status in patients with colorectal cancer is important for identifying the appropriate treatment protocol. In the Pathology Artificial Intelligence Platform (PAIP) 2020 challenge, artificial intelligence researchers were invited to predict MSI status based on colorectal cancer slide images. Participants were required to perform two tasks. The primary task was to classify a given slide image as belonging to either the MSI-high or the microsatellite-stable group. The second task was tumor area segmentation to avoid ties with the main task. A total of 210 of the 495 participants enrolled in the challenge downloaded the images, and 23 teams submitted their final results. Seven teams from the top 10 participants agreed to disclose their algorithms, most of which were convolutional neural network-based deep learning models, such as EfficientNet and UNet. The top-ranked system achieved the highest F1 score (0.9231). This paper summarizes the various methods used in the PAIP 2020 challenge. This paper supports the effectiveness of digital pathology for identifying the relationship between colorectal cancer and the MSI characteristics.
Somatic TP53 single nucleotide variants, indels and copy number alterations in chronic myelomonocytic leukemia (CMML)
Authors: Mark Gurney, Abhishek A. Mangaonkar, Terra Lasho, Christy Finke, Aref Al-Kali, Naseema Gangat, Mithun V. Shah, Hassan B. Alkhateeb, Ayalew Tefferi, David Sallman, Zhuoer Xie, David Viswanatha, Kaaren Reichard, Najla Al Ali, Rami Komrokji, Eric Padron, Mrinal M. Patnaik
Journal: Leukemia (2023)
Medicare’s Plan for Drug-Price Negotiation — The Importance of Defining Generic Entry
Authors: Stacie B. Dusetzina, Nancy L. Keating, Haiden A. Huskamp, Michelle M. Mello
Journal: New England Journal of Medicine (2023)

The Inflation Reduction Act allows CMS to negotiate prices for a small number of Medicare-covered drugs. Identifying opportunities to proactively address potential gaming of this authority is important.